The reductive conversion of ribonucleotides to deoxyribonucleotides, catalyzed by ribonucleotide reductase is a crucial and rate limiting reaction in the DNA biosynthetic pathway. Therefore this reaction represents a logical target for cancer chemotherapy. In the response to the need for an effective agent at this site, a series of ribonucleotide reductase inhibitors based on a vicinal polyhydroxyphenyl structure have been developed. The compound of the initial series with the best antitumor activity in animal tumor models is 3,4-dihydroxybenzohydroxamic acid (147). Tests directed by the National Cancer Institute have shown the compound to significantly extend the life span of leukemia bearing mice and reduce the tumor size of several of the solid tumor models. Further solid tumor tests with more optimal doses and scheduling will be performed to determine the extent of effectiveness against slow growing tumors. The compounds have as a basis of their biochemical action, free radical scavenging activity. This property suggests the use of VF 147 in combination with other anticancer agents whose deleterious effects are related to the formation of a toxic free radical. Therefore combination of VF147 and doxorubicin is expected to be synergistic. Due to the biochemical reaction that is inhibited it is also expected to be synergistic with cyclophosphamide. If these premises prove correct the support for toxicology study preliminary to clinical trials for VF 147 should be obtainable. The successful research results of the best first generation compound will be extended to the best agent of the second generation compounds (VF236). In particular we will measure effectiveness against solid tumor models, utility in combination chemotherapy with cyclophosphamide and doxorubicin, and free radical activity.